Inferring chromatin-bound protein complexes from genome-wide binding assays.

TitleInferring chromatin-bound protein complexes from genome-wide binding assays.
Publication TypeJournal Article
Year of Publication2013
AuthorsGiannopoulou EG, Elemento O
JournalGenome Res
Date Published2013 Aug
KeywordsChromatin, Chromatin Immunoprecipitation, Cluster Analysis, Computational Biology, Gene Expression Regulation, Genome, Human, Humans, Models, Genetic, Protein Binding, Regulatory Sequences, Nucleic Acid, Sequence Analysis, DNA, Transcription Factors

Genome-wide binding assays can determine where individual transcription factors bind in the genome. However, these factors rarely bind chromatin alone, but instead frequently bind to cis-regulatory elements (CREs) together with other factors thus forming protein complexes. Currently there are no integrative analytical approaches that can predict which complexes are formed on chromatin. Here, we describe a computational methodology to systematically capture protein complexes and infer their impact on gene expression. We applied our method to three human cell types, identified thousands of CREs, inferred known and undescribed complexes recruited to these CREs, and determined the role of the complexes as activators or repressors. Importantly, we found that the predicted complexes have a higher number of physical interactions between their members than expected by chance. Our work provides a mechanism for developing hypotheses about gene regulation via binding partners, and deciphering the interplay between combinatorial binding and gene expression.

Alternate JournalGenome Res.
PubMed ID23554462
PubMed Central IDPMC3730103